Oxidized cellulose suture



Jan, l 1951 .1.1. EBERL OXIDIZED CELLULOSE SUTURE 2 Sheets-Sheet l Filed March 24, 1949 N 6 me w w s am w a CM In m G mp 2 @d 5 M M 5 4x INVENTOR C72/w55 ffies/P4.

E y i ATTORNEY Jam 16, 1951 1. J. EBERL 2,537,978

OXIDIZED CELLULOSE SUTURE Filed March 24, 1949 2 Sheets-Sheet 2 o .z 4 e s lo lz :4 le rs zo 22 24 za 2s so az s4 as sew Patented Jan. ld, 1951 OXIDIZED CELLULOSE SUTUBE James J. Eben, chester, ra., animano Etnico@ Suture Laboratories Incorporated, a corporation of New Jersey Application March 24, 1949, Serial No. 83,107

3 Claims. (Cl. 12S-335.5)

This invention relates to absorbable sutures made from oxidized cellulose threads. i

Most absorbable sutures heretofore used have been of the catgut variety, although actually made from sheep intestines. These are nonhomogeneous both as to strength and digestibility, due to differences in the structure of the sheeps intestines from end to end, differences in individual sheep, and seasonal variations. The best known manufacturing processes are uneconomical because of the low yields that are obtained and the high labor costs that are entailed.

These disadvantages are absent with oxidized cellulose sutures made in accordance with the instant invention. The improved sutures also possess many advantages in their own right. For example, the digestion time of an oxidized cellulose suture, i. e., the time required for the suture to disintegrate in human tissue may be fairly accurately controlled by adjusting the degree of oxidation. A surgeon's knot made with an oxidized cellulose suture has less tendency to slip than is the case with catgut. Such sutures are potentially less irritating to the tissue since they do not behave like dead tissue in the human system. They are non-proteinous in nature and hence do not provide a culture medium for saprophytic organisms. Their use thus reduces the chance of infection. Many other advantages inherent in the improved suture will be evident as the description of the invention proceeds.

It has been discovered in accordance with the inventionV that sutures meeting U. S. Pharmacopoeia standards as regards tensile strength, and strength over a surgeons knot may be prepared by oxidizing strands of substantially pure cellulose to diierent degrees depending upon the ultimate rate of absorption the suture is to possess when in use, provided the initial strength and character of the cellulose thread or strand is such that after the oxidation processes, suilicient strength remains in the various categories to satisfy suture requirements.

According to U. S. Pharmacopoeia standards,

catgut sutures of good quality possess a dry tensile i strength in the neighborhood of 2 grams per denier. Knot strength requirements range from 1.0 to 1.4 grams per denier, the lower value relating to the smaller sizes of catgut (Nos. 00000 and 0000) and the higher value to the larger sizes.

Absorption time for catgut, i. e., the period required for digestion in the human system, does not carry a U. S. P. designation. Catgut is merely classified as Type A Plain, Type C Medium Chromic and Type D Extra Chromic. Type C, under ordinary conditions in the striate muscle, retains its integrity from to 20 days and Type A and Type D a shorter and a longer period of time respectively. However, the absorption rate of catgut depends to some extent upon the condition of the patient, absorption being most rapid in a healthy man and slowest in young. aged, tubercular and anemie patients. In mucous membranes. the digestion rate is about four4 times as fast as in muscular tissue.

Oxidized cellulose sutures may be made in accordance with the invention having rates of digestion fully equivalent to catgut. Actually the digestion rate of the improved sutures may be forecast with greater accuracy than is possible for catgut since that of the former, at least to the point of zero strength, depends upon the pH of the body tissue whereas that of the latter depends solely on enzymatic attack. The pH is substantially constant from person to person and is yalso more constant throughout the body than is enzyme distribution.

The improved sutures may be oxidized with periodic acid. The oxidizing action is selective to produce oxidized cellulose threads of definite and predictable characteristics and which will disintegrate by hydrolysis at the pH of' body tissue.V

When cellulose is oxidized with periodic acid, the action produces a scission of the glucose ring to form aldehyde groups from the secondary alcohols. The formula for this reaction is as Hoorn- Hocus-: ono

\ c o l) JI) Further reaction converts the aldehyde groups (CHO) to carboxyl groups, but this is undesirable since the resultant product is immune to hydrolysis. It may be avoided by controlling the rate of oxidation.

In the accompanying drawings:

Fig. 1 are curves showing the rate of oxidation of cellulose thread for dierent concentrations of periodic acid.

Fig. 2 is a perspective view of a reel for holding thread during a periodic oxidation, and

Fig. 3 is a curve showing the rate of digestion in a buffer solution of pH '7.5 of a cellulose suture oxidized with periodic acid.

The degree of oxidation is controlled by using a periodic acid solution of a given strength and varying the reaction time during which the cellulose thread is exposed to the oxidizing medium. In Fig. 1 there are shown curves representing per cent oxidation plotted against reaction time in hours for the oxidation of one gram of cellulose with ml. of periodic acid at 50 C. for three typical concentrations expressed as normality (N), namely, .224N, .108N. and .096N. As will be observed, the rate of oxidation increases with an increase in the concentration of the periodic acid Ybe After allowing about two plete reduction of the periodic periodic acid are given in action of periodic acid. A suitable reel is illustrated in Fig. 2 and comprises a rod-like body portion 20 presenting hooks 2| at its opposite ends about which the thread is wound. Such reels are preferred since the oxidation and auch subsequent processing as is necessary can be carried out without removing the thread from the reel. Preferably, the thread is wound loosely on the reel to allow for shrinkage during oxidation.

The oxidation is carried out merely by immersing the thread in the periodic acid solution the requisite time to give the desired degree or per cent of oxidation. After the desired time of oxidation, the thread is immediately removed from thorough washing, it is preferred to remove the last traces of periodic acid by a suitable reducing agent as, for instance, an aqueous solution of sodium thiosulfate.

acid, the suture reel is dipped into alcohol and dried under vacuum. The purpose of this drying procedure is to remove the water as fast as possible to minimize loss in strength from slow hydrolysis. When the sutures are wound on reels during the oxidation process they ma dried without removal therefrom.

The results obtained by oxidizing various t of cellulose thread with Table I In other Concentration of Periodic Acid m n r :D 1526 niagnfo Ilona msmmu lzxazLLL LLLLLL arri, 2li e iii r. Alun im .me

um r f 232950529686 24.4138 42J1 .43.5. mmmmw Laaaaaaarrrr 2222i 2222 321 P m T i w1.

t, A 444444444444. E R Sumawnwaw S aw 51.1. men L 5..n..5.w.m5.5.5..o.5.5. W A 33 0333 W 3333 444. gmmim U T L mn.

n .Mmmm m n w H N l S TZ R m M m E M w 1. H m 52 .l2 8 l. weon/.G 2 30 L 00 m u mmmnamwmmmum N m @mamma N awww m ...1. m U LLLLLLLLLLLL M T N 1. 1.....11 I D R M m m 0 C e., F awmwmnamana o mmmmww e di. mmmmmmmmmmmm F 0.0.nwwnwmm mh .m 1

8 s 8 mmmmmmmmmmmm Mmmm@ 3 solution. In general. the higher concentrations are preferred since, for the same degree of oxidation, the resulting sutures are stronger. words, the higher the rate of oxidation, the less the sutures are subject to loss of strength through g hydrolysis.

The degree to which a thread is oxidized by periodic acid may be determined by titrating 'an aliquot of the solution of periodic acid at the end of the oxidizing reaction. The determination is 10 based on the liberation of iodine upon neutralizing the excess acidity.

The number of mini-equivalents of periodic acid consumed per gram of cellulose is then calculated from the difference in the normality of the periodic acid and washed with water. After a control solution and a solution containing the sample. Since 12.34 milli-equivalents are required for complete oxidation. the per cent oxidation is easily obtained.

All of the examples of oxidation with periodic hours for a com acid solutions herein given were carried out with acids prepared from Frederick Smith Co., reagent and buffered to a pH of 4.6 with sodium acetate. The ratio of cellulose thread vto solution was, in each case, 1 to 50 and all treatments were carried 25 out in an oven regulated at 50 C. While it is not absolutely essential, it is preferred that the cellulose threads be wound on small reels made o1' glass or any other suitable material, such as stainless steel, which like glass is inert to the the following table:

l The diameters oi the threads in this group are proportional to denier and range between .011 and .013. i The diameters oi the threads in this group are proportional to denier and range between .012 and .013.

'I'he results tabulated above show that oxidized regular Fortisan which has about 8 twists per inch satisfies suture requirements in all strength categories up to about 25% oxidation where wet and dry strength start to fall olf. Indeed. the strength characteristics in the range mentioned are superior to catgut in all categories. Hightwist Fortisan (10 twists per inch), high-twist v cotton to 20 twists per inch), low-twist cotton (10 twists per inch)V and linen were entirely satisfactory in the oxidation ranges tested. Fortisan, one of the materials referred to in Table I, is the trade name for a pure cellulose thread which, during its manufacture. has passed through a cellulose acetate stage. After the cellulose fiber has been spun,'it is hydrolized by steam and stretched. This thread, which may be obtained from the Perfect Thread Company of Brooklyn, New York, was used in the periodic acid oxidations in addition to cotton and linen thread.

The absorbability of oxidized cellulose sutures, i. e.. the length of time they retain their integrity in use depends upon their degree of oxidation. Within the range of oxidation that produces acceptable sutures as regards strength, a range of oxidation may be selected that will result in a suture having a rate of digestion equivalent to catgut. The rate of digestibility of such sutures may be obtained by soaking the sutures in a solution which simulates body conditions as. for instance, a phosphate solution buffered to pH 7.5 (pH of tissue) and maintained at a temperature of 37 C. Such a solution may be prepared as follows:

1000 cc. Nad-113041211220 containing 23.88 g./llter 178.3 cc. KHzPOi containing 9.078 g./liter In Fig. 3 there is plotted by way of illustration only, the rate of digestion for oxidized sutures made from Fortisan. In the figure, per cent oxidation is plottedagalnst days required to go to zero strength. The curve shows that the time required for sutures cf this character to go to zero strength ranges from one day for sutures oxidized to approximately 31 to about thirty-six days for sutures oxidized in the neighborhood of 15%.

With this information one may select the proper percentage of oxidation to produce a suture which will digest to zero strength in a desired period of time. Similar determinations may be made for sutures made from other types of cellulose and for cellulose sutures which have been oxidized with periodic acid of different concentrations. Indeed, because of the many variables involved such as initial tensile strength, source and characteristics of the cellulose thread, the specific action of the oxidizing agent on the thread, the concentration of the oxidizing agents, etc., it is practically impossible to give all of the information that would be necessary in every instance to produce a suture of given digestive life at body pH. However, from the information given and the various modifications of the invention described, one skilled in the art will readily be able to do this.

6 The standards for tensile strength of catgut sutures as given in the U. S. Pharmacopoeia are arbitary and not necessarily applicable to sutures of" the type comprehended herein. The dry tensile strengths of the improved sutures are, in many instances, superior to catgut. But, even when dry strength is inferior, wet strength. which actually is the most important factor, is oftentimes superior to catgut. Because of the many factors involved, it is quite impossible to arbitrarily place a numerical value on the lower limit of tensile strength the treated suture should possess. Any cellulose thread, treated in the manner described and which is strong enough to perform the function of a suture is within the scope of the invention. In the claims, therefore, this strength factor has been termed suture tenacity.

It is also relatively difficult to fix quantitatively the maximum degree of oxidation for the cellulose thread. Therefore, in the claims, the degree of oxidation has been defined as that which will cause the thread to proceed to zero strength at the pH of body tissue (7.3-7.5) in not less than the period of time required for normal healing of a sutured wound, that is, in a period of at least live days. It might. be added here that only rarely would it be desirable to prepare a suture having a digestion rate of less than five days.

The invention has been described in its pref'erred embodiments, but many modifications thereof are included within its spirit. It is to be limited, therefore, only by the scope of the appended claims.

This application is a continuation-impart of my application Serial No. 577,309 filed February 10. 1945, now abandoned.

What is claimed is:

1. A thread of suture tenacity comprising cellulose oxidized selectively to convert secondary alcohol groups to aldehyde groups, the oxidation being suiiicient to cause the reduction of the thread to zero strength lat the pH of body tissue (7.3-7.5) in a period oi at least five days.

2. A thread of suture tenacity comprising cellulose oxidized by periodic acid sufilciently to cause its reduction to zero strength at the pH of body tissue (7.3-7.5) in'a period of at least nve days.

3. A thread of suture tenacity comprising ce1- lulose oxidized with periodic acid by converting secondary alcohol groups to aldehyde groups to an extent not greater than 20% of the theoretical oxidation with periodic acid, oxidation to this extent being suilicient to cause the reduction of the thread to zero strength at the pH of body tissue (7.3-7.5) in a period of at least five days.

` JAMES J. EBERL.

REFERENCES CITED 4UNIL'IED STATES PATENTS Name Date Yackel et al. lieb. 25, i941 Number 

1. A THREAD OF SUTURE TENACITY COMPRISING CELLULOSE OXIDIZED SELECTIVELY TO CONVERT SECONDARY ALCOHOL GROUPS TO ALDEHYDE GROUPS, THE OXIDATION BEING SUFFICIENT TO CAUSE THE REDUCTION OF THE THREAD TO ZERO STRENGTH AT THE PH OF BODY TISSUE (7.3-7.5) IN A PERIOD OF AT LEAST FIVE DAYS. 